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1.
Fish Shellfish Immunol ; 118: 147-154, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34487827

RESUMO

Previous studies show that some ribosomal proteins perform immune effector functions via killing bacteria directly. However, it remains largely unknown about other effector functions of ribosomal proteins during a bacterial infection. In this study, we expressed and purified four ribosomal proteins of the amphioxus Branchiostoma japonicum, termed rBjRPS15, rBjRPS18, rBjRPS19 and rBjRPS30-precursor (rBjRPS30P). They all exhibited bactericidal activity against Gram-positive Staphylococcus aureus, and with the exception of rBjRPS19 and rBjRPS30P, were capable of killing Gram-negative Escherichia coli. Importantly, rBjRPS15, rBjRPS19 and rBjRPS30P were able to agglutinate S. aureus in the presence of Mg2+, but none of them could agglutinate E. coli even in the presence of Mg2+ or Ca2+. Moreover, the S. aureus agglutination was achieved by the binding of these three proteins to the peptidoglycan component of the bacterial cell wall. This is the first report showing that some ribosomal proteins possess bacterial agglutinating activity, and these data provide a new angle to the roles of ribosomal proteins in immune defense.

2.
Arch Microbiol ; 203(9): 5621-5633, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34459930

RESUMO

Owing to the prominent capabilities of bioconversion and biosynthesis, A. terreus has become attractive in biotechnical and pharmaceutical industry. In this work, an Aspergillus strain with potential antibacterial activities, was isolated from sponge in South China Sea. Based on the morphological and phylogenetic analysis, the strain was identified as A. terreus B12. Via the Illumina MiSeq sequencing platform, the complete genome was obtained, showing a genetic richness of biosynthetic gene clusters (BGCs), which might underpin the metabolic plasticity and adaptive resilience for the strain. Genome mining identified 67 BGCs, among which, 6 gene clusters could allocate to known BGCs (100% identity), corresponding to diverse metabolites like clavaric acid, dihydroisoflavipucine/isoflavipucine, dimethylcoprogen, alternariol, aspterric acid, and pyranonigrin E. Moreover, a range of compounds was isolated from B12 fermentation, e.g., terrein, butyrolactone I, terretonin A&E, acoapetaline B, and epi-aszonalenins A. Of note, acoapetaline B and epi-aszonalenins A, which had been respectively reported in plants and A. novofumigatus but with scarce information, was unexpectedly obtained from this species for the first time. The genomic and metabolic heterogeneity observed in strain B12, should be at least partially attributed to the genetic variability and biochemical diversity of A. terreus, which could be an interesting issue open to future efforts.

3.
Diagnostics (Basel) ; 11(7)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34359334

RESUMO

A new concept for the diagnosis and management of non-functional dyspepsia in guidelines was lacking in the past decade. Medical advancement has proven pancreatic fibrosis (essential image evidence of early chronic pancreatitis) to be a cause of dyspepsia and related to pancreatic exocrine dysfunction. This study aimed to analyze the clinical picture, biomarker, and percentage of pancreatic fibrosis in the dyspeptic population. A total of 141 consecutive patients were retrospectively enrolled. They were diagnosed with peptic ulcer disease, 9.2% (n = 13); pancreatic fibrosis, 17% (n = 24); pure Helicobacter pylori infection, 19.9% (n = 28); functional dyspepsia, 53.2% (n = 75); and chronic pancreatitis, 0.7% (n = 1). Among those with pancreatic fibrosis, (n = 24), 11 were diagnosed on the basis of a pancreatic acoustic radiation force impulse exceeding 1.4 m/s, and the remaining 13 were diagnosed with early chronic pancreatitis with at least three of the Japanese endoscopic ultrasonography criteria. The anatomic distribution of parenchymal criteria of early chronic pancreatitis was head, 53%; body, 38%; and tail, 9%. There were 17 cases (71%, 17/24) without Helicobacter pylori and whose dyspepsia improved after pancreatic enzyme replacement with a ratio of 82.3% (14/17). Of the 141 cases, 19 received gastric emptying scintigraphy and Western blot analysis of chromogranin-A in duodenal mucosa. Delayed gastric emptying was more common in functional dyspepsia and chromogranin-A was expressed more in pancreatic fibrosis. In conclusion, pancreatic fibrosis (including early chronic pancreatitis) outnumbered peptic ulcer disease in the dyspeptic population and pancreatic enzyme therapy was effective for 82% of cases. In early chronic pancreatitis, pancreatic fibrosis is dominant in the head location, and duodenum mucosa chromogranin-A is a potential biomarker with increased expression in an age-matched manner.

4.
Sci Total Environ ; 790: 147990, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34380243

RESUMO

The plasticizer di(2-ethylhexyl) phthalate (DEHP) and its hydrolysate mono(2-ethylhexyl) phthalate (MEHP) are major toxicants from plastics, but their association with hormone-dependent cancers has been controversial. We treated the human ovarian cancer cell lines SKOV3 and A2780 with low concentrations of DEHP/MEHP, and found that although no significant effect on cell proliferation was observed, ovarian cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT) were promoted by submicromolar MEHP but not DEHP. Next, ovarian cancer patient data from The Cancer Genome Atlas (TCGA) were obtained and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) supported enrichment and Kaplan-Meier survival analyses, which identified PI3K/Akt pathway as a pivotal signaling pathway in ovarian cancer. We found that 500 nM MEHP treatment significantly increased PIK3CA expression, which could be reversed by the knockdown of peroxisome proliferator-activated receptor alpha (PPARα). Silencing PIK3CA significantly suppressed the MEHP-induced migration, invasion and EMT. In addition, we validated that MEHP treatment promoted phosphorylation of Akt and degradation of IκB-α, thereby activating NF-κB and enhancing NF-κB nuclear translocation. In nude mice, MEHP exposure significantly promoted the metastasis of ovarian cancer xenografts, which could be suppressed by the treatment of PPARα inhibitor GW6471. Our findings showed that low-dose MEHP promoted ovarian cancer progression through activating PI3K/Akt/NF-κB pathway, in a PPARα-dependent manner.


Assuntos
Dietilexilftalato , Neoplasias Ovarianas , Animais , Linhagem Celular Tumoral , Dietilexilftalato/análogos & derivados , Dietilexilftalato/toxicidade , Feminino , Humanos , Camundongos , Camundongos Nus , NF-kappa B , Neoplasias Ovarianas/induzido quimicamente , PPAR alfa/genética , Fosfatidilinositol 3-Quinases , Ácidos Ftálicos , Proteínas Proto-Oncogênicas c-akt
5.
Cancer Sci ; 112(8): 3243-3254, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34097350

RESUMO

RNA N6 -methyladenosine (m6 A) is an emerging regulatory mechanism for tumor progression in several types of cancer. However, the underlying regulation mechanisms of m6 A methylation in colorectal cancer (CRC) remain unknown. Although the oncogenic function of methyl CpG binding protein 2 (MeCP2) has been reported, it is still unclear whether MeCP2 could alter RNA m6 A methylation state. Here, we systematically identified MeCP2 as a prometastasis gene to regulate m6 A methylation in CRC. Interestingly, MeCP2 could bind to methyltransferase-like 14 (METTL14) to coregulate tumor suppressor Kruppel-like factor 4 (KLF4) expression through changing m6 A methylation modification. Furthermore, insulin-like growth factor 2 mRNA-binding protein 2 recognized the unique modified m6 A methylation sites to enhance KLF4 mRNA stability. Taken together, these findings highlight the novel function of MeCP2 for regulating m6 A methylation and reveal the underlying molecular mechanism for the interaction between MeCP2 and METTL14, which offers a better understanding of CRC progression and metastasis.


Assuntos
Adenosina/análogos & derivados , Neoplasias Colorretais/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Proteína 2 de Ligação a Metil-CpG/metabolismo , Metiltransferases/genética , Regulação para Cima , Adenosina/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Camundongos , Transplante de Neoplasias , Estabilidade de RNA
6.
Artigo em Inglês | MEDLINE | ID: mdl-33804696

RESUMO

With the development of unstable footwear, more research has focused on the advantages of this type of shoe. This type of shoe could improve the muscle function of the lower limb and prevent injury risks in dynamic situations. Therefore, the purpose of this study was to investigate differences in lower-limb kinetics and kinematics based on single-leg landing (SLL) using normal shoes (NS) and bionic shoes (BS). The study used 15 male subject volunteers (age 23.4 ± 1.14 years, height 177.6 ± 4.83cm, body weight (BW) 73.6 ± 7.02 kg). To ensure the subject standardization of the participants, there were several inclusion criteria used for selection. There were two kinds of experimental shoes used in the landing experiment to detect the change of lower limbs when a landing task was performed. Kinetics and kinematic data were collected during an SLL task, and statistical parametric mapping (SPM) analysis was used to evaluate the differences between NS and BS. We found that the flexion and extension angles of the knee (p = 0.004) and hip (p = 0.046, p = 0.018) joints, and the dorsiflexion and plantarflexion of ankle (p = 0.031) moment were significantly different in the sagittal planes. In the frontal plane, the eversion and inversion of the ankle (p = 0.016), and the abduction and adduction of knee (p = 0.017, p = 0.007) angle were found significant differences. In the horizontal plane, the external and internal rotation of hip (p = 0.036) and knee (p < 0.001, p = 0.029) moment were found significant differences, and knee angle (p = 0.043) also. According to our results, we conclude that using BS can cause bigger knee and hip flexion than NS. Also, this finding indicates that BS might be considered to reduce lower-limb injury risk during the SLL phase.


Assuntos
Biônica , Sapatos , Adulto , Fenômenos Biomecânicos , Humanos , Joelho , Articulação do Joelho , Masculino , Projetos Piloto , Amplitude de Movimento Articular , Adulto Jovem
7.
Hum Vaccin Immunother ; 17(8): 2736-2747, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-33787459

RESUMO

Objective: To evaluate the awareness of College Students (CSs) of HPV vaccine in China and provide evidence-based recommendations for HPV vaccine's publicity and promotion.Methods: Web of Science, PubMed, Science of Direct, EBSCO, China National Knowledge Infrastructure and Wanfang Data were searched. A random effects meta-analysis was conducted to determine pooled estimates of Awareness Rate (AR) for HPV vaccine.Results: Of the 36 studies included, the estimated AR of HPV vaccine was 40.27% (95% CI: 30.86%, 50.06%) among Chinese CSs. The AR of HPV vaccine was stratified by factors as gender, major, area, city, survey time, and sampling method of the study. The pooled AR of HPV vaccine among CSs was as follows: 44.17% (95% CI: 31.65%, 57.09%) and 31.93% (95% CI: 13.25%, 54.30%) for females and males; 44.47% (95% CI: 29.90%, 59.55%) and 12.02% (95% CI: 7.69%, 17.15%) for medical-related and nonmedical majors; 44.47% (95% CI: 28.71-60.82%) and 41.16% (95% CI: 26.48-56.64%) for Eastern and Midwestern region; 48.86% (95% CI: 30.63-67.25%) and 33.19% (95% CI: 22.27-45.12%) for first-tier and second- and third-tier city; 29.67 (95% CI: 11.44-52.16%) and 38.81 (95% CI: 27.14-51.21%) for AR before and after HPV vaccine entered in China; 51.51% (95% CI: 32.21%, 70.53%) and 26.21% (95% CI: 17.41%, 36.10%) for nonrandom and random sampling.Conclusion: This review indicates that awareness of HPV vaccine among CSs remains relatively low in China compared with European countries. Our findings may provide useful information to better understand the HPV vaccine awareness status among Chinese CSs.

8.
Int Urol Nephrol ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686532

RESUMO

OBJECTIVE: The LC-MS/MS-based non-targeted metabolomics method was used to differentially screen serum and urine metabolites of acute kidney injury (AKI) patients and healthy people, to explore potential biomarkers of AKI and analyze related pathways, and explain the potential mechanism and biological significance of AKI. METHODS: The serum and urine samples from 30 AKI patients and 20 healthy people were selected to conduct a non-targeted metabolomics study by ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). The differential metabolites between the two groups were searched by the human metabolome (HMDB) database ( https://hmdb.ca/ ) and the related pathways of these potential biomarkers were identified by searching the Kyoto encyclopedia of genes and genomes (KEGG) database ( https://www.kegg.jp/ ). The total metabolic pathways were analyzed by the MS Peaks to Pathways module of MetaboAnalyst ( https://www.metaboanalyst.ca/ ). RESULTS: Multivariate data analysis found that serum and urine metabolism in AKI patients was significantly different from healthy people. We found three metabolites in urine (2-S-glutathionyl glutathione acetate, 5-L-Glutamyl-taurine, and L-Phosphoarginine) contributing to the separation of AKI patients from healthy people, and major metabolic pathways associated with these potential biomarkers including cytochrome P450 metabolism, arginine, and proline metabolism. CONCLUSION: 2-S-glutathionyl glutathione acetate, 5-L-Glutamyl-taurine, and L-Phosphoarginine were associated with AKI patients, which could be selected as potential biomarkers to predicate AKI disease.

9.
Nanotechnology ; 32(19): 195708, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33629667

RESUMO

Morphological tuning or additional cation doping is one of the potential and simple methods to enhance the photocatalytic properties of ceria, in which rare-earth element doped ceria nanorods (CeO2-RE NRs) are expected to be a promising photocatalyst with high activity. But the optimal doping conditions, including the variety and concentration of RE elements are ambiguous, and the contribution of doped RE ions to the enhancement of photocatalytic activity needs to be further studied. In this work, we doped La, Y and Sm with a wide range of 0%-30% into CeO2 NRs, and investigated the phase, morphology, band gap, oxygen vacancy concentration, PL spectra and photocatalytic activity variation under different doping conditions. All synthesized CeO2-RE NRs possessed a good nanorod morphology except the 15 and 30% Y-doped samples. The energy band gaps of the synthesized samples changed slightly; the 10% CeO2-RE NRs with the narrowest band gaps possessed the higher photocatalytic performance. The most outstanding photocatalyst was found to be the 10% Y-doped CeO2 NRs with a methylene blue photodegradation ratio of 85.59% and rate constant of 0.0134 min-1, which is particularly associated with a significant higher oxygen vacancy concentration and obviously lower recombination rate of photogenerated e-/h+ pairs. The doped RE ions and the promotion of oxygen vacancy generation impede the recombination of photogenerated carriers, which is proposed as the main reason to enhance the photocatalytic property of CeO2.

10.
Nanotechnology ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33494076

RESUMO

Morphology tuning or additional cations doping is one of the potential and simple methods to enhance the photocatalytic property of ceria, in which rare-earth elements doped ceria nanorods (CeO2-RE NRs) are expected to be a promising photocatalyst with high activity. But the optimal doping conditions including variety and concentration of RE elements are ambiguity, and the contribution of doped RE ions on the enhancement of photocatalytic activity needs to be further concerned either. In this work, we doped La, Y and Sm with a wide range of 0 - 30 % into CeO2 NRs, and investigated the phase, morphology, band gap, oxygen vacancies concentration, PL spectra and photocatalytic activity variation under different doping conditions. All synthesized CeO2-RE NRs own well-shaped nanorod morphology except the 15 and 30 % Y doped samples. The energy band gaps of synthesized samples change slightly, the 10 % of CeO2-RE NRs with the narrowest band gaps own the higher photocatalytic performance. The most outstanding photocatalyst is found as the 10 % Y doped CeO2 NRs with the methylene blue photodegradation ratio of 85.59 % and the rate constant of 0.0134 min-1, which is particularly associated with a significant higher oxygen vacancies concentration and obviously lower recombination rate of photogenerated e-/h+ pairs. The doped RE ions and the promoting oxygen vacancies generation impede the recombination of photogenerated carrier, which is proposed as the main reason to enhance the photocatalytic property of CeO2.

11.
Cancer Sci ; 112(1): 178-193, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33058325

RESUMO

Although anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has achieved great success in some cancers, most colorectal cancer (CRC) patients remain unresponsive. Therefore, further clarification of the underlying mechanisms is needed to improve the therapy. In this study, we explored the distinct functions of different PD-L1 alternative splicing isoforms in CRC. We investigated the biological functions in PD-L1 knocked down/knockout cells, which were verified through overexpression of PD-L1 isoforms a, b, and c. The roles of PD-L1 isoforms in immune surveillance resistance was also analyzed. Meanwhile, we performed RNA-seq to screen the downstream molecules regulated by PD-L1 isoforms. Finally, we detected PD-L1 and PD-L1 isoforms levels in a cohort of serum samples, two cohorts of CRC tissue samples, and analyzed the correlation of PD-L1 isoforms with PD-1 blockade therapy response in two clinical CRC cases. The results indicated that PD-L1 knockout inhibited proliferation, migration, and invasion, and isoform b exerted a more significant inhibitory effect on T cells than the other two isoforms. Moreover, isoform c could promote CRC progression through regulating epithelial-mesenchymal transition. Clinical data showed that CRC patients with positive PD-L1 expression were associated with poorer overall survival. High serum PD-L1 level was associated with poor prognosis. The level of isoform b or c was negatively associated with prognosis, and a higher level of isoform b was associated with a good response to anti-PD-1 therapy. In conclusion, isoform b should be considered as a biomarker for clinical responsiveness to anti-PD-1/PD-L1 immunotherapy; isoform c had a prometastatic role and is a new potential target for CRC therapy.


Assuntos
Processamento Alternativo/genética , Antígeno B7-H1/genética , Neoplasias Colorretais/genética , Isoformas de Proteínas/genética , Animais , Biomarcadores Tumorais/genética , Linhagem Celular , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Células HCT116 , Células HT29 , Humanos , Imunoterapia/métodos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos Nus/genética , Camundongos SCID , Prognóstico
12.
Clin Neurol Neurosurg ; 200: 106364, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33348302

RESUMO

OBJECTIVE: To investigate the preoperative psychological distress in the primary caregivers of glioma patients and its influencing factors and to determine the relationship between preoperative psychological states of glioma patients and their caregivers. METHODS: Using a mixed methods design, the caregivers of patients with malignant glioma were interviewed and completed questionnaires about anxiety/depression and family function during preoperative period. RESULTS: Caregivers of glioma patients had different types of psychological distress before surgery. A total of 46 caregivers (36.5 %) had preoperative psychological depression or anxiety symptom; 30 caregivers (23.8 %) had depression symptoms, 39 caregivers (31.0 %) had anxiety symptoms, and 23 (18.3 %) had both preoperative anxiety and depression symptoms. Female gender was an influential factor for both preoperative depression and anxiety symptoms in caregivers, surgical information was a risk factor for caregivers' preoperative depression symptoms and residence was a risk factor for caregivers' preoperative anxiety symptoms. The preoperative psychological states of patients was positively correlated with the preoperative anxiety and depression symptoms of caregivers. CONCLUSION: The rural female caregivers are more likely to experience psychological distress before surgery, and the preoperative psychological states of patients was positively correlated with the psychological distress in caregivers.


Assuntos
Neoplasias Encefálicas/psicologia , Cuidadores/psicologia , Glioma/psicologia , Cuidados Pré-Operatórios/psicologia , Angústia Psicológica , Autorrelato , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Estudos Transversais , Feminino , Glioma/diagnóstico , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Adulto Jovem
13.
Brain Behav ; 10(9): e01771, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32790154

RESUMO

PURPOSE: Behavioral symptoms, including depression, anxiety, and cognitive impairment, are common clinical symptoms of patients with glioma. However, the mechanisms underlying the behavioral symptoms of glioma patients remain unclear. In this study, we explore the correlation between markers of systemic inflammation and preoperational behavioral symptoms in glioma patients. PATIENTS AND METHODS: Patients (n = 71) who had recently undertaken imaging (i.e., CT, MRI) for suspected glioma had a face-to-face interview, completed self-report scales, and provided blood samples. Furthermore, we tested blood samples by a protein chip to select differential inflammatory cytokines and further confirm such differences using liquid-phase chip technology. RESULTS: The prevalence of depression, anxiety, and cognitive impairment in glioma patients prior to surgery in this study was 53.5%, 70.4%, and 32.4%, respectively. The increased levels of IFN-γ were positively correlated with clinical symptoms of depression in the glioma patients. Moreover, increased IL-2 levels were negatively associated with anxiety symptoms (p = .00) and positively correlated with cognitive impairment in glioma patients. CONCLUSION: This study suggests that systemic inflammation is associated with behavioral symptoms in glioma patients. This provides further evidence of the contribution of inflammatory markers to psychological symptoms in the context of physical conditions and lays the foundation for the development of further treatments of the behavioral symptoms in glioma patients.


Assuntos
Disfunção Cognitiva , Glioma , Ansiedade/etiologia , Disfunção Cognitiva/etiologia , Depressão/etiologia , Glioma/complicações , Humanos , Inflamação
14.
Materials (Basel) ; 13(15)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32731578

RESUMO

This study aimed to investigate the effect of Mg treatment on the nucleation and ostwald growth of inclusions. Deoxidized experiments with Al (0.05%Al) and Al-Mg (0.05%Al + 0.03%Mg) were carried out at 1873 K, and the composition, number, and size of inclusions were studied as a function of holding time. Homogeneous nucleation theory and ostwald ripening were utilized to calculate the nucleation rate, the critical size of nuclei, and coarsening rate of inclusions. The results show that small inclusions were more easily found in the steels with Al-Mg complex deoxidation, and the number of inclusions with Al-Mg complex deoxidation is larger at an early stage of deoxidation. The critical size of nuclei increases in the order of MgAl2O4 (0.3-0.4 nm) < Al2O3 (0.4-0.6 nm), and the nucleation rate increases in the order of Al2O3 (1100 cm-3 s-1) < MgAl2O4 (1200 cm-3s-1), which is consistent with the experimental results. Moreover, the coarsening rate of MgAl2O4 inclusions was smaller than Al2O3 inclusions in both the value of kd(cal.) from ostwald growth and the value of kd(obs.) from inclusion size. The effect of Mg addition on coarsening of inclusion was analyzed and their mechanism was discussed based on ostwald ripening theory and Factsage calculation.

15.
J Pathol ; 250(2): 217-230, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31650548

RESUMO

Aberrant expression of forkhead box C1 (FOXC1) promotes tumor metastasis in multiple human malignant tumors. However, the upstream modulating mode and downstream molecular mechanism of FOXC1 in metastasis of colorectal cancer (CRC) remain unclear. Herein we describe a systematic analysis of FOXC1 expression and prognosis in CRC performed on our clinical data and public databases, which indicated that FOXC1 upregulation in CRC samples was significantly associated with poor prognosis. FOXC1 knockdown inhibited migration and invasion, whereas FOXC1 overexpression caused the opposite phenotype in vitro and in vivo. Furthermore, MMP10, SOX4 and SOX13 were verified as the target genes of FOXC1 for promoting CRC metastasis. MMP10 was demonstrated as the direct target and mediator of FOXC1. Interestingly, Ser241 and Ser272 of FOXC1 were identified as the key sites to interact with p38 and phosphorylation, which were critically required for maintaining the stability of FOXC1 protein. Moreover, FOXC1 was dephosphorylated by protein phosphatase 2A and phosphorylated by p38, which maintained FOXC1 protein stability through inhibiting ubiquitination. Expression of p38 was correlated with FOXC1 and MMP10 expression, indirectly indicating that FOXC1 was regulated by p38 MAPK. Therefore, FOXC1 is strongly suggested as a pro-metastatic gene in CRC by transcriptionally activating MMP10, SOX4 and SOX13; p38 interacts with and phosphorylates the Ser241 and ser272 sites of FOXC1 to maintain its stability by inhibiting ubiquitination and degradation. In conclusion, the protein stability of FOXC1 mediated by p38 contributes to the metastatic effect in CRC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Neoplasias Colorretais/metabolismo , Fatores de Transcrição Forkhead/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia , Animais , Autoantígenos/metabolismo , Movimento Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , DNA de Neoplasias/genética , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/secundário , Metaloproteinase 10 da Matriz/metabolismo , Camundongos Nus , Invasividade Neoplásica , Fosforilação , Prognóstico , Fatores de Transcrição SOXC/metabolismo , Fatores de Transcrição SOXD/metabolismo , Regulação para Cima
16.
Adv Sci (Weinh) ; 6(23): 1901114, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832310

RESUMO

Frameshift mutations frequently occur in colorectal cancer (CRC) with microsatellite instability (MSI), but the nature and biological function of many MSI-associated mutations remain elusive. Here, an MSI frameshift mutation is identified in glioma tumor suppressor candidate region gene 1 (GLTSCR1) that produces two C-terminal-truncated proteins. Additionally, GLTSCR1 is verified as a tumor suppressor that inhibits CRC metastasis. Through binding to bromodomains and the phosphorylation-dependent interaction domain of bromodomain protein 4 (BRD4) via the C-terminus, GLTSCR1 blocks oncogenic transcriptional elongation. However, truncated GLTSCR1 translocates into the cytoplasm and loses BRD4 binding domain, which induces the phosphorylation of RNA Pol II at Ser2 and dephosphorylation at Ser5, then increases oncogenic transcriptional elongation. Importantly, GLTSCR1 deficiency decreases sensitivity to bromodomain and extra terminal domain inhibitors. This study highlights the molecular mechanism of the GLTSCR1-BRD4 interaction, which is a potential therapeutic target for CRC.

17.
Sci Rep ; 9(1): 10616, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337832

RESUMO

Autologous vascular grafts have the advantages of better biocompatibility and prognosis. However, previous studies that implanted bare polymer tubes in animals to grow autologous tubular tissues were limited by their poor yield rates and stability. To enhance the yield rate of the tubular tissue, we employed a design with the addition of overlaid autologous whole blood scaffold containing lipopolysaccharides (LPS). Furthermore, we applied in vivo dynamic mechanical stimuli through cyclically inflatable silicone tube to improve the mechanical properties of the harvested tissues. The effectiveness of the modification was examined by implanting the tubes in the peritoneal cavity of rats. A group without mechanical stimuli served as the controls. After 24 days of culture including 16 days of cyclic mechanical stimuli, we harvested the tubular tissue forming on the silicone tube for analysis or further autologous interposition vascular grafting. In comparison with those without cyclic dynamic stimuli, tubular tissues with this treatment during in vivo culture had stronger mechanical properties, better smooth muscle differentiation, and more collagen and elastin expression by the end of incubation period in the peritoneal cavity. The grafts remained patent after 4 months of implantation and showed the presence of endothelial and smooth muscle cells. This model shows a new prospect for vascular tissue engineering.


Assuntos
Enxerto Vascular/métodos , Animais , Aorta/diagnóstico por imagem , Aorta/transplante , Autoenxertos , Western Blotting , Colágeno/metabolismo , Elastina/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Silicones , Tecidos Suporte , Ultrassonografia
18.
Sci Rep ; 9(1): 3670, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30842535

RESUMO

The characteristics of particles greatly affect the microstructure and performance of metallic materials, especially their sizes. To provide insight into coarsening phenomena of particles in metallic melts, Fe-O-Al-Ca melt with calcium aluminate particles was selected as a model system. This study uses HT-CSLM, SEM detections and stereological analysis to probe the behavior of particles and their characteristics including size, number density, volume fraction, spreading of particle size, inter-surface distance and distribution of particles. Based on the experimental evidence and calculation of collision, we demonstrate that the coarsening of inclusion particles is not only dependent on the Ostwald growth as studied in previous study, but also on the particle coagulation, and floatation. The collision of particles affects the maximum size of the particles during whole deoxidation process and dominates the coarsening of particles at later stage of deoxidation under the condition without external stirring in Fe-O-Al-Ca melts. The factors influencing collision behaviors and floating properties were also analyzed, which is corresponding to coarsening behavior and change of particle characteristic in the melts with different amounts of Ca addition. Such coarsening mechanism may also be useful in predicting the size of particles in other metallic materials.

19.
Sci Rep ; 8(1): 1135, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29348615

RESUMO

Tremendous focus has been put on the control of particle size distribution which effects the grain structure and mechanical properties of resulting metallic materials, and thus nucleation and growth of particles in solution should be clarified. This study uses classical nucleation theory and Ostwald ripening theory to probe the relationship between the compositions of Fe-O-Al-Ca melts and the behavior of particles under the condition of no external stirring. Our experimental data suggest that decreasing the initial Ca addition and Al addition is conductive to the increase of nucleation rate for calcium aluminate particles, which exhibits a same change trend with that predicted from classical nucleation theory. Based on the experimental evidence for particles size distribution in three-dimensional, we demonstrate that Ostwald ripening is the predominate mechanism on the coarsening of particles in Fe-O-Al-Ca melt at early stage of deoxidation under the condition of no external stirring but not at later stage.

20.
Eur J Pharmacol ; 818: 569-577, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29162431

RESUMO

Wound healing is one of the major complications of diabetes, and problems with wound healing in diabetics often lead to amputation and even death. AMP-activated protein kinase (AMPK) is a protein involved in intracellular metabolism. Activated AMPK can reduce visceral fat and cholesterol synthesis and even inhibit hepatic gluconeogenesis. Activation of AMPK has been widely used in the treatment of type II diabetes. We applied an AMPK activator (Adenine) to human fibroblasts and to the wounds of streptozotocin-induced diabetic mice. We applied Adenine ointment to the wounds on 7 consecutive days and observed the healing status as well as activation of AMPK and angiogenic factors. Based on the appearance of the wounds, the results showed that after 7 days of treatment the wound area was smaller in the Adenine-treated group relative to the control group. The results for tissue protein expression showed that, compared to the control group, angiogenic related protein, PPARδ were increased and receptor for advanced glycation endproducts (RAGE) was decreased in the Adenine-treated group. Our studies indicate that Adenine has the potential to become a useful drug in the treatment of diabetic wound healing.


Assuntos
Adenina/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Neovascularização Fisiológica/efeitos dos fármacos , PPAR delta/metabolismo , Cicatrização/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Linhagem Celular , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Ativação Enzimática/efeitos dos fármacos , Humanos , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
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